Antimicrobial resistance is now recognized as a top public health threat in critical need of innovation. Our translational research focuses on the pharmacodynamics of antimicrobials in the treatment of complex bacterial infections. We identify novel ways to employ antibiotics in patients to combat antimicrobial resistance development and treatment failure. This is done using a laboratory bench-to-bedside approach that encompasses multidisciplinary research collaborations in the basic science, medicine, and pharmacy disciplines. We focus primarily on antimicrobial dosing and combinations to treat multi-drug resistance Gram-positive infections, such as methicillin-resistant Staphylococcus aureus. We focus on three major themes related to this topic in both the laboratory and clinic: (1) novel combination approaches to improve antibacterial activity (2) anti-virulence strategies to reduce bacterial pathogenicity, and (3) host-pathogen immunologic response in the presence of antibiotics. Our goal is to identify a precision approach, in terms of both the patient and bacteria, to better utilize antibiotics, minimize resistance development, and optimize patient outcomes.
Berti AD, Baines SL, Howden BP, Sakoulas G, Nizet V, Proctor RA, Rose WE. Heterogeneity of genetic pathways toward daptomycin nonsusceptibility in Staphylococcus aureus determined by adjunctive antibiotics. Antimicrob Agents Chemother, 2015 May;59(5):2799-806.
Berti AD, Theisen E, Sauer JD, Nonejuie P, Olson, J, Pogliano J, Sakoulas G, Nizet V, Proctor RA, Rose WE. Penicillin binding protein 1 is important in the compensatory response of Staphylococcus aureus to daptomycin-induced membrane damage and is a potential target for β-lactam-daptomycin synergy Antimicrob Agents Chemother 2015 Nov 2;60(1):451-8.
Rose WE, Eickhoff JC, Shukla, SK, Pantrangi MH, Rooijakkers S, Cosgrove SE, Nizet V, Sakoulas G. Serum Concentration of interleukin-10 (IL-10) At time of hospital admission Is predictive of mortality in patients with Staphylococcus aureus bacteremia. J. Infect Dis. 2012 Nov 15;206(10):1604-11.
Shukla SK, Rose W, Schrodi SJ. Complex host genetic susceptibility to Staphylococcus aureus infections. Trends Microbiol. 2015 Sep;23(9):529-36.
Gagetti P, Pasteran F, Martinez MP, Fatouraei M, Gu J, Fernandez R, Paz L, Rose WE, Corso A, Rosato AE. Modeling meropenem treatment, alone and in combination with daptomycin, for KPC-producing Klebsiella pneumoniae with unusually low carbapenem MICs. Antimicrob Agents Chemother. 2016 Jul 22;60(8):5047-50.